Computational reduction vaccine for covid-19 bin100

ABSTRACT

A system for the rapid development of vaccines or anti-bacterial drugs is required when working with pandemics. The easiest way to formulate these new vaccines is through computational reduction of existing organisms via statistical models. Once vaccine candidates are arrived at through this method, “Super Organisms” containing all of the computationally reducible fragments can then be taken through a Crispr reduction process wherein those computationally reducible fragments are removed. The result is a vaccine candidate which has possible problematic function partially or fully removed. The “neutered” version of the virus can be tested in a lab and in clinical trials for efficacy. This patent covers a vaccine candidate utilizing computationally reducible fragments 100 base pairs or greater in length; those fragments removed from future Covid-19 Super Organisms either collectively (as in this patent) or individually; as well as the RNA transcripts of those fragments.

BACKGROUND OF THE INVENTION

The present invention focuses on a computational reduction vaccine for Covid-19 with reduction fragments larger than 100 base pairs.

A computational reduction vaccine may be defined herein as a vaccine candidate which is arrived at by removing various non-repetitive fragments in a virus or bacteria first computationally, then via Crispr in an a “Super-Organism” (an organism which contains all, or the majority, of those fragments), and then utilizing the remaining organism as a traditional “live” or “dead” vaccine, which even though marginally computationally reduced, is still recognizable by the human immune system as an invader and therefore provokes a useful immune response. That immune response then shields the recipient from the actual virus going forward.

It is now possible via Python modules such as Numpy (numerical Python) and Biopython (a module specifically designed for computationally manipulating DNA sequences), to analyze in great detail and with great speed thousands, or even millions of sequence records available through the NIH GenBank databases.

Those computational methods are not herein described, but the statistical analysis below will illustrate the efficacy of the method in determining the frequency of various structures, as well as the ability to track those structures though time. It is along those two lines—frequency of appearance, and consistency of appearance, across an entire genetic database that one can derive vaccine candidates computationally.

The traditional way to do this would be to remove each fragment or structure via Crispr one by one and test the resulting organism for problematic function. Once problematic function was discovered, use the resulting live or dead virus in a vaccine. However, in the case of Covid-19, where solutions are demanded in shorter time frames, it is more efficient to simply remove all potential problematic function fragments via various fragment length groups in order to create one or two potential vaccine candidates instead of hundreds. This is the first of two such vaccines.

BRIEF DESCRIPTION OF SEVERAL VIEWS OF THE DRAWINGS

FIG. 1 a table of computational fragment reductions from Covid-19 which are longer than 100 base pairs. From left to right, you have the “Bin” size, or size of the fragments; the number of appearances of the fragment across the entire Covid-19 database; the appearance percent of the fragment expressed as a decimal; the Record ID for the reference organism in which the fragment was first found; and the “strip” or fragment (each of which is listed below) which when removed from a Covid-19 Super Organism or Base Organism will give us a vaccine.

FIG. 2 is a SnapGene circular view of Covid-19 sample MT370902.1 from which this vaccine is derived.

FIG. 3 is the same SnapGene circular view of MT370902.1 with the fragments outlined below removed.

DETAILED DESCRIPTION OF THE INVENTION

There are several types of vaccines. This invention introduces a new type of vaccine which is a computationally derived reductive vaccine. A computationally derived reductive vaccine utilizes statistical computation to arrive at a list of fragments which can then be removed from live viruses or bacteria via Crispr to arrive at “neutered” versions which can then form the basis for the vaccine.

Computational reduction in this case may be defined as non-laboratory computational reduction of organisms into fragments, which then can be assessed on the basis of frequency across an entire range of similar organisms as well as computationally tested to confirm that those structures are unique to the virus or bacteria in question. The particulars of the method of discovery for these fragments is proprietary.

What is not proprietary is the statistical analysis of the fragments which are outlined in FIG. 1 and below. In the case of this particular vaccine candidate, the fragments which are included are longer than 100 base-pairs and appear in the NIH Covid-19 database greater than 32% of the time. The Covid-19 database “snapshot” from which the fragments in this patent were selected was taken on Jun. 16, 2020 at 5:41 am. That database is available upon request.

The result of this patent is relatively simple. When a “Super Organism” or Covid-19 sample which contains all, or most, of the fragments outlined below is found, that Super Organism can then be genetically modified in a laboratory using Crispr to remove those fragments. Once all those fragments are removed from the organism, it can then be tested to see if problematic function remains.

“Problematic function” in the case of Covid-19 is two-fold: functions of the virus which cause high transmissibility rates, and functions of the virus which cause high mortality rates. It may take us years to figure out exactly what those functions are and where they appear exactly on the genetic assay. This patent provides a shortcut by simply removing all of the most likely candidates for those problematic functions by identifying fragments which appear often enough not to be considered mutations (i.e. fragments only appearing in one or two samples).

The scan of the entire database of Covid-19 provides 18 fragments longer than 100 base pairs which appear more than 32% of the time across the entire database. These fragments are unique to Covid-19 and cannot be found in any other virus in the NIH GenBank databases. Those 18 fragments are listed below. Each fragment table lists the NIH organism Record ID, number of appearances of that identical fragment in the Covid-19 reference database, appearance percentage expressed as a decimal, and the fragment.

Fragment 1:

Organism: MT459910.1 Number of Appearances across NIH Covid-19 database on Jun. 16, 2020: 3919 Percentage Appearance (decimal): 99.52% Fragment: TTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAG GAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTC AACCT

Fragment 2:

Organism: MT539159.1 Number of Appearances across NIH Covid-19 database on Jun. 16, 2020: 3917 Percentage Appearance: 99.47% Fragment: TTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAG GAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTC AACCTGTGCTTGTGAAATT

Fragment 3:

Organism: MT601279.1 Number of Appearances across NIH Covid-19 database on Jun. 16, 2020: 3916 Percentage Appearance: 99.44% TTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAG GAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTC AACCTGTGCTTGTGAAATTG

Fragment 4:

Organism: MT365025.1 Number of Appearances across NIH Covid-19 database on Jun. 16, 2020: 3914 Percentage Appearance: 99.39% GCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGA TGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGT T

Fragment 5:

Organism: MT520346.1 Number of Appearances across NIH Covid-19 database on Jun. 16, 2020: 3909 Percentage Appearance: 99.26% TTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTG GGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACA AATT

Fragment 6:

Organism: MT365025.1 Number of Appearances across NIH Covid-19 database on Jun. 16, 2020: 3905 Percentage Appearance: 99.16% TTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGG AAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAA CCTGTGCTTGTGAAATTGTCGGTGGACAAATT

Fragment 7:

Organism: MT365025.1 Number of Appearances across NIH Covid-19 database on Jun. 16, 2020: 3904 Percentage Appearance: 99.14% GTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCT ATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATT TA

Fragment 8:

Organism: MT365025.1 Number of Appearances across NIH Covid-19 database on Jun. 16, 2020: 3895 Percentage Appearance: 98.91% ACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGC AATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATT GAACTTTCATTAAT

Fragment 9:

Organism: MT365025.1 Number of Appearances across NIH Covid-19 database on Jun. 16, 2020: 3894 Percentage Appearance: 98.88% ACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCA TATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTA

Fragment 10:

Organism: MT481895.1 Number of Appearances across NIH Covid-19 database on Jun. 16, 2020: 3874 Percentage Appearance: 98.37% CTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAG AATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTA GTGCGT

Fragment 11:

Organism: MT477856.1 Number of Appearances across NIH Covid-19 database on Jun. 16, 2020: 3871 Percentage Appearance: 98.30% CCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGG GAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCAC ACGCCTATTAATTTAGT

Fragment 12:

Organism: MT365025.1 Number of Appearances across NIH Covid-19 database on Jun. 16, 2020: 3867 Percentage Appearance: 98.20% CCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGG GAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCAC ACGCCTATTAATTTAGTGCGT

Fragment 13:

Organism: MT259269.1 Number of Appearances across NIH Covid-19 database on Jun. 16, 2020: 3867 Percentage Appearance: 98.20% CCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGG GAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCAC ACGCCTATTAATTTAGTGCG

Fragment 14:

Organism: MT451142.1 Number of Appearances across NIH Covid-19 database on Jun. 16, 2020: 2634 Percentage Appearance: 66.89% TTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGG TGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGT

Fragment 15:

Organism: MT510694.1 Number of Appearances across NIH Covid-19 database on Jun. 16, 2020: 2633 Percentage Appearance: 66.86% GCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAA GGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGT

Fragment 16:

Organism: MT365025.1 Number of Appearances across NIH Covid-19 database on Jun. 16, 2020: 2613 Percentage Appearance: 66.35% TGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGA TGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAAC TCAATATGAGTATGGT

Fragment 17:

Organism: MT499174.1 Number of Appearances across NIH Covid-19 database on Jun. 16, 2020: 1266 Percentage Appearance: 32.15% TGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTCTACCCTCCAGA TGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAAC TCAATATGAGT

Fragment 18:

Organism: MT365026.1 Number of Appearances across NIH Covid-19 database on Jun. 16, 2020: 1265 Percentage Appearance: 32.12% TGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTCTACCCTCCAGA TGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAAC TCAATATGAGTATGGT

Additionally, it is possible to state that the most likely vaccine candidate fragments in more targeted versions of this patent are Fragments 14-16, as they appear in approximately 70% of the database, but not in nearly all samples which would include early (non-transmissible, low-fatality) Covid-19 organisms.

In creation of the vaccine candidate we can also view that vaccine not only as a reductive entity which can be manufactured from a variety of possible starting organisms, but also as a complete organism which has potentially been “neutered” of its destructive features.

In order to arrive at that possibility, we must first find a Covid-19 sample which contains all of these structures. Of the 3,898 complete Covid-19 sequences in the Jun. 16, 2020 Covid-19 database, there are 2,462 which contain the above sequences, and 1,525 which contain the maximum of 17 of the 18 of those sequences. However, since there is some overlap between fragments, only 8 need be removed.

So to create a reductive vaccine, computationally those fragments are removed to create the vaccine candidate as shown in this patent's sequence file. The original reference sequence is also included and can also be downloaded from NIH via the reference MT370902.1. As previously stated, there are also 2,467 other reference candidates which could be used as Super Organisms or Base Organisms for the next generation of vaccines. That list is available upon request.

This application also seeks to cover the RNA transcript of each of the fragments. It may well be that RNA transcript vaccines based on these fragments would be of equal or greater efficacy in triggering a useful immune response.

It should also be noted that these fragments are 100 base pairs or greater, which means a fragment has only a 1 in 1.60 novemdecillion (4¹⁰⁰) chance of occurring—in the entire history of the planet. In other words, even at a 32% recurrence rate across the entire Covid-19 genome, these fragments represent viable mathematical targets for vaccines.

This application identifies 18 such fragments.

Claims moved to separate file

Abstract moved to separate file. 

Having described my invention herein, I claim:
 1. The reference fragments as “key fragments” which may be computationally removed from 2,462 Covid-19 “Super Organisms” (as of Jun. 16, 2020) to form potential vaccine candidates without laying claim to the actual fragments as genetic material, only their use, collectively or individually, as the basis for the creation of a new organism or organisms including a “neutered” Covid-19 live or dead virus which may be potentially used safely as a vaccine following Crispr reduction, and laboratory testing, and clinical trials.
 2. The newly created organism with these fragments removed as shown in the sequence file which is a vaccine candidate for Covid-19 as well as future refinements of same wherein those fragments may be removed collectively, or individually, to create an effective Covid-19 vaccine from other Covid-19 samples, and which includes future refinements of the vaccine wherein the removal of only one or several of these fragments may be required.
 3. The RNA transcript of each of the fragments described herein which individually or collectively can be utilized in the same manner as in claim 1 without requiring the subtraction of the fragments from a Super Organism for the creation of a live or dead vaccine but rather can be utilized in a kind of “shotgun” approach wherein all fragments are included en masse in each dose of the vaccine, or future refinements of same wherein after significant laboratory testing only one or two RNA transcripts of the fragments may need to be utilized. 